Le Sclerosis functional Composite; ” Treatment differences were calculated using ANCOVA. doi

Le Sclerosis functional Composite; ” Treatment differences were calculated using buy Nafarelin ANCOVA. doi:10.1371/journal.pone.0086663.t003 group, all AEs were classified as mild or moderate. There was no severe or serious AE. In the IFNB-1b group, AEs were classified as mild or moderate except for one patients with a foot fracture that was classified as a severe as well as serious AE. Discussion Atorvastatin 40 mg added to IFNB-1b did not have any beneficial effect on RRMS compared to IFNB-1b monotherapy over a period of 24 months. There were no significant differences in the primary or secondary endpoints between the two treatment groups. Non-siginificant trends were due to baseline differences and not treatment. The combination of atorvastatin and IFNB-1b was well tolerated and did not cause unexpected or severe side effects. All AEs were similar in both groups. Especially clinical relevant elevated 22948146 liver enzymes did not occur more frequently in the atorvastatin/IFNB-1b group and unlike in the core study no dose adaptation of atorvastatin was necessary. The results of the SWABIMS and SWABIMS Extension study are in line with several other combination trials of statins and IFNB in RRMS . In this regard, there is actually no evidence to support the use of either atorvastatin or simvastatin as an adjunctive therapy to IFNB in RRMS. Adding atorvastatin or simvastatin to IFNB resulted to be safe and well tolerated without the occurance of serious side effects. In addition, SWABIMS and the SWABIMS extension study do not indicate a harmful effect of atorvastatin in addition to IFNB-1b on the course of RRMS as well. This, however, is still controversial due to individual data suggesting it. The safe and well tolerated use of statins in combination with IFNB in MS patients is of importance because MS patients with vascular risk factors and vascular disease have a more rapid disability progression than MS patients without. SWABIMS and the SWABIMS Extension Study in conjunction with other CASIN custom synthesis studies suggest that atorvastatin and simvastatin can be used for prevention of vascular events in MS patients who need a lipidlowering therapy. These conclusions on atorvastatin and simvastatin are likely to apply for other statins as well given the comparable immunomodulatory properties of the different statins in experimental studies. However, this has to be proven in separate clinical studies. In contrast to the negative clinical studies, statins and IFNB have additive anti-inflammatory and immunomodulatory effects in vitro. A possible explanation for this contradiction could be antagonistic effects of both drugs. Statins inhibit the STAT1 phosphorylation which is an important signaling pathway for IFNB, antagonize the inhibitory effect of IFNB on the proteolytic activity on MMP-2 and MMP-9, and reduce IFNB function and type 1 interferon responses in RRMS patients. However, the question whether statins alone or in combination with other MS therapeutics could be beneficial in MS has not been studied and has yet to be answered. Statins have anti-inflammatory and immunomodulatory effects in experimetal studies including studies in ��Experimental allergic encephalomyelitis”, the animal model of MS. Furthermore, an openlabel, single-arm study evaluating simvastatin 80 mg/d in 30 RRMS patients showed a significant decrease in the number and volume of Gd-enhancing lesions. A recent randomized, double-blind, placebo-controlled phase II trial, that is not published yet, showed a.Le Sclerosis functional Composite; ” Treatment differences were calculated using ANCOVA. doi:10.1371/journal.pone.0086663.t003 group, all AEs were classified as mild or moderate. There was no severe or serious AE. In the IFNB-1b group, AEs were classified as mild or moderate except for one patients with a foot fracture that was classified as a severe as well as serious AE. Discussion Atorvastatin 40 mg added to IFNB-1b did not have any beneficial effect on RRMS compared to IFNB-1b monotherapy over a period of 24 months. There were no significant differences in the primary or secondary endpoints between the two treatment groups. Non-siginificant trends were due to baseline differences and not treatment. The combination of atorvastatin and IFNB-1b was well tolerated and did not cause unexpected or severe side effects. All AEs were similar in both groups. Especially clinical relevant elevated 22948146 liver enzymes did not occur more frequently in the atorvastatin/IFNB-1b group and unlike in the core study no dose adaptation of atorvastatin was necessary. The results of the SWABIMS and SWABIMS Extension study are in line with several other combination trials of statins and IFNB in RRMS . In this regard, there is actually no evidence to support the use of either atorvastatin or simvastatin as an adjunctive therapy to IFNB in RRMS. Adding atorvastatin or simvastatin to IFNB resulted to be safe and well tolerated without the occurance of serious side effects. In addition, SWABIMS and the SWABIMS extension study do not indicate a harmful effect of atorvastatin in addition to IFNB-1b on the course of RRMS as well. This, however, is still controversial due to individual data suggesting it. The safe and well tolerated use of statins in combination with IFNB in MS patients is of importance because MS patients with vascular risk factors and vascular disease have a more rapid disability progression than MS patients without. SWABIMS and the SWABIMS Extension Study in conjunction with other studies suggest that atorvastatin and simvastatin can be used for prevention of vascular events in MS patients who need a lipidlowering therapy. These conclusions on atorvastatin and simvastatin are likely to apply for other statins as well given the comparable immunomodulatory properties of the different statins in experimental studies. However, this has to be proven in separate clinical studies. In contrast to the negative clinical studies, statins and IFNB have additive anti-inflammatory and immunomodulatory effects in vitro. A possible explanation for this contradiction could be antagonistic effects of both drugs. Statins inhibit the STAT1 phosphorylation which is an important signaling pathway for IFNB, antagonize the inhibitory effect of IFNB on the proteolytic activity on MMP-2 and MMP-9, and reduce IFNB function and type 1 interferon responses in RRMS patients. However, the question whether statins alone or in combination with other MS therapeutics could be beneficial in MS has not been studied and has yet to be answered. Statins have anti-inflammatory and immunomodulatory effects in experimetal studies including studies in ��Experimental allergic encephalomyelitis”, the animal model of MS. Furthermore, an openlabel, single-arm study evaluating simvastatin 80 mg/d in 30 RRMS patients showed a significant decrease in the number and volume of Gd-enhancing lesions. A recent randomized, double-blind, placebo-controlled phase II trial, that is not published yet, showed a.